Interleukin-12 (IL-12) is a proinflammatory cytokine that induces the production of interferon-gamma (IFN-γ), promotes the differentiation of T helper-1 (Th1) cells and connects innate and adaptive immune response pathways (Trinchieri, Nat Rev Immunol (2003) 3:133). IL-12 is produced by dendritic cells (DC) and phagocytes (e.g., macrophages, neutrophils, immature dendritic cells) in response to pathogens during infection (Id.). Structurally, IL-12 is a heterodimeric protein comprised of two polypeptide chains, a p35 chain and a p40 chain (Airoldi, et al., Haematologica (2002) 87:434-42). IL-12 is structurally related to at least two other heterodimeric proinflammatory cytokines, interleukin-23 (IL-23) and interleukin-27 (IL-27) (Hunter, Nat Rev Immunol (2005) 5:521; and Vandenbroeck, et al., J Pharm Pharmacol (2004) 56:145).
Cytokines, including IL-12, play a critical role as molecular adjuvants for vaccines to induce improved immune responses. IL-12 has been shown to increase the magnitude of vaccine-induced immune responses (see, for example, Tomioka, Curr Pharm Des (2004) 10:3297; El-Aneed, Eur J Pharmacol (2004) 498:1; Stevceva, Curr Pharm Des (2005) 11:801; and Toka, et al, Immunol Rev (2004)199:100). To provide IL-12 as molecular adjuvant, it is important to develop efficient expression vectors and efficiently expressing coding nucleic acid sequences for this cytokine. The present invention addresses this need.